The goal of this research is to define the basic immunology of serum IgA, with particualr attention to its role as a modulator of the secondary effects of the immune response such as excessive complement activation, and to study its role in producing susceptibility to blood stream invasion by Gram-negative bacteria. The model used will be disseminated disease due to N. meningitidis. Serum IgA has been shown to inhibit or block immune lysis of N. meningitidis by IgM and IgG and to be present in quantities sufficient to completely abrogate bactericidal activity in the sera of patients early in the course of invasive meningococcal disease. The molecular basis of this inhibition will be sought in the binding affinity of the respective Ig classes. Acquisition of IgA will be studied in relation to epidemic occurrence of meningococcal disease.